Application of immunohistochemical, ultrastructural and morphologic techniques revealed conclusive evidence for the origin of chemically-induced papillary lung tumors of the mouse from alveolar cells rather than from bronchiolar Clara cells, as reported by some investigators. These controversial tumors were found to be of alveolar origin based on specific antigen localization and unique ultrastructural features found only in alveolar Type II cells. In contrast, chemically induced bronchiolar tumors of the Syrian hamster were found to arise from bronchiolar Clara cells by the use of similar techniques, although progressive evidence of de- differentiation was also found. A sensitive ABC immunohistochem- ical technique was developed to detect lentiviral antigens in autopsy and biopsy specimens of humans with human immunodeficiency virus (HIV) infection and monkeys with simian immunodeficiency virus (SIV) infection. Monoclonal and polyclonal antisera to HIV and SIV proteins detected viral gag proteins in inflammatory macrophages and giant cells, tumor cells, endothelial cells and bone marrow cells. Thus, our technique was very sensitive for detecting infected cells for diagnosis and studies of the pathogenesis of the associated diseases and tumors. Immunohistochemical studies of human tissues with HIV and cytomegalovirus (CMV) infection led to detailed immunoblotting studies which revealed that the major gag protein of HIV and major capsid protein of CMV cross-react. Antisera to H-ras p21 detected the antigen in fixed tissue sections of Harvey sarcomas on the cell membrane in T24 cells, and in the cytoplasm of some normal tissues and in liver tumors of mice that contain an activated H-ras oncogene. Immunoblotting used to detect p21 in comparison with levels detected by immunohistochemistry, revealed that one monoclonal antibody claimed to react with p21 did not react to p21 or with rodent tumors with an activated H-ras oncogene. Interpretation of published studies involving p21 immunohistochemistry require caution and additional study.